Skip to main content Accessibility help

Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer’s disease

  • Javier Oltra-Cucarella (a1) (a2), Miriam Sánchez-SanSegundo (a1), Darren M. Lipnicki (a3), John D. Crawford (a3), Richard B. Lipton (a4), Mindy J. Katz (a4), Andrea R. Zammit (a4), Nikolaos Scarmeas (a5) (a6), Efthimios Dardiotis (a7), Mary H. Kosmidis (a8), Antonio Guaita (a9), Roberta Vaccaro (a9), Ki Woong Kim (a10) (a11) (a12), Ji Won Han (a10), Nicole A. Kochan (a3), Henry Brodaty (a3) (a13), José A. Pérez-Vicente (a2), Luis Cabello-Rodríguez (a2), Perminder S. Sachdev (a3) (a13), Rosario Ferrer-Cascales (a1) and Cohort Studies of Memory in an International Consortium (COSMIC) (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a8) (a9) (a10) (a11) (a12) (a13)...



To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.


4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.


All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 – 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.


Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.


Corresponding author

Correspondence should be addressed to: Rosario Ferrer-Cascales, Department of Health Psychology, University of Alicante, Campus de San Vicente del Raspeig s/n, San Vicente del Raspeig, Alicante 03690, Spain. Phone: +34 965 90 34 00 Ext. 9420. Email:


Hide All
Albert, M. S. et al. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 270279. doi: 10.1016/j.jalz.2011.03.008.
Artero, S., Petersen, R. C., Touchon, J. and Ritchie, K. (2006). Revised criteria for mild cognitive impairment: validation within a longitudinal population study. Dementia and Geriatric Cognitive Disorders, 22, 465470. doi: 10.1159/000096287.
Azuero, A. (2016). A note on the magnitude of hazard ratios: correspondence. Cancer, 122, 12981299. doi: 10.1002/cncr.29924.
Beekly, D. L. et al. (2007). The National Alzheimer’s Coordinating Center (NACC) database: the uniform data set. Alzheimer Disease & Associated Disorders, 21, 249258. doi: 10.1097/WAD.0b013e318142774e.
Bonner-Jackson, A., Mahmoud, S., Miller, J. and Banks, S. J. (2015). Verbal and non-verbal memory and hippocampal volumes in a memory clinic population. Alzheimer’s Research & Therapy, 7, 61. doi: 10.1186/s13195-015-0147-9.
Burke, D. L., Ensor, J. and Riley, R. D. (2017). Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ. Statistics in Medicine, 36, 855875. doi: 10.1002/sim.7141.
Crowther, M. J., Look, M. P. and Riley, R. D. (2014). Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis. Statistics in Medicine, 33, 38443858. doi: 10.1002/sim.6191.
Dardiotis, E., Kosmidis, M. H., Yannakoulia, M., Hadjigeorgiou, G. M. and Scarmeas, N. (2014). The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): rationale, study design, and cohort description. Neuroepidemiology, 43, 914. doi: 10.1159/000362723.
Didic, M. et al. (2013). Impaired visual recognition memory predicts Alzheimer’s disease in amnestic mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 35, 291299. doi: 10.1159/000347203.
Dierckx, E. et al. (2009). Verbal cued recall as a predictor of conversion to Alzheimer’s disease in mild cognitive impairment. International Journal of Geriatric Psychiatry, 24, 10941100. doi: 10.1002/gps.2228.
Ferreira, L. K., Diniz, B. S., Forlenza, O. V., Busatto, G. F. and Zanetti, M. V. (2011). Neurostructural predictors of Alzheimer’s disease: a meta-analysis of VBM studies. Neurobiology of Aging, 32, 17331741. doi: 10.1016/j.neurobiolaging.2009.11.008.
Guaita, A. et al. (2013). Brain aging and dementia during the transition from late adulthood to old age: design and methodology of the “Invece.Ab” population-based study. BMC Geriatrics, 13, 98. doi: 10.1186/1471-2318-13-98.
Hoffman, J. M. et al. (2000). FDG PET imaging in patients with pathologically verified dementia. Journal of Nuclear Medicine, 41, 19201928.
Katz, M. J. et al. (2012). Age-specific and sex-specific prevalence and incidence of mild cognitive impairment, dementia, and Alzheimer dementia in blacks and whites: a report from the Einstein aging study. Alzheimer Disease & Associated Disorders, 26, 335343. doi: 10.1097/WAD.0b013e31823dbcfc.
Kawas, C. H. et al. (2003). Visual memory predicts Alzheimer’s disease more than a decade before diagnosis. Neurology, 60, 10891093. doi: 10.1212/01.WNL.0000055813.36504.BF.
Kim, M. J. et al. (2011). Cortical thinning in verbal, visual, and both memory-predominant mild cognitive impairment. Alzheimer Disease & Associated Disorders, 25, 242249. doi: 10.1097/WAD.0b013e3182076d31.
Kim, T. H. et al. (2013). Overview of the Korean Longitudinal Study on Cognitive Aging and Dementia. Alzheimer’s & Dementia, 9, P626P627. doi: 10.1016/j.jalz.2013.05.1268.
Larrieu, S. et al. (2002). Incidence and outcome of mild cognitive impairment in a population-based. Neurology, 59, 15941599. doi: 10.1212/01.WNL.0000034176.07159.F8.
Marcus, C., Mena, E. and Subramaniam, R. M. (2014). Brain PET in the diagnosis of Alzheimer’s disease. Clinical Nuclear Medicine, 39, e413e426. doi: 10.1097/RLU.0000000000000547.
McKhann, G. M., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34, 93993944. doi: 10.1212/WNL.34.7.939.
McKhann, G. M. et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 263269. doi: 10.1016/j.jalz.2011.03.005.
Mistridis, P., Krumm, S., Monsch, A. U., Berres, M. and Taylor, K. I. (2015). The 12 years preceding mild cognitive impairment due to Alzheimer’s disease: the temporal emergence of cognitive decline. Journal of Alzheimer’s Disease, 48, 10951107. doi: 10.3233/JAD-150137.
Mitchell, A. and Shiri-Feshki, M. (2009). Rate of progression of mild cognitive impairment to dementia: meta-analysis of 41 robust inception cohort studies. Acta Psychiatrica Scandinavica, 119, 252265. doi: 10.1111/j.1600-0447.2008.01326.x.
Moye, J. (1997). Nonverbal memory assessment with designs: construct validity and clinical utility. Neuropsychology Review, 7, 157170. doi: 10.1023/B:NERV.0000005907.34499.43.
Oltra-Cucarella, J. et al. (2018). Using the base rate of low scores helps to identify progression from amnestic MCI to AD. Journal of the American Geriatrics Society, 66, 13601366. doi: 10.1111/jgs.15412.
Petersen, R. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256, 183194. doi: 10.1111/j.1365-2796.2004.01388.x.
Petersen, R. et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 19851992. doi: 10.1001/archneur.58.12.1985.
Petersen, R. et al. (2010). Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology, 74, 201209. doi: 10.1212/WNL.0b013e3181cb3e25.
Petersen, R., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G. and Kokmen, E. (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303308. doi: 10.1001/archneur.56.3.303.
Richardson, J. T. E. (2011). Eta squared and partial eta squared as measures of effect size in educational research. Educational Research Review, 6, 135147. doi: 10.1016/j.edurev.2010.12.001.
Ritchie, K. et al. (2017). The midlife cognitive profiles of adults at high risk of late-onset Alzheimer’s disease: the PREVENT study. Alzheimer’s & Dementia, 13, 10891097. doi: 10.1016/j.jalz.2017.02.008.
Sachdev, P. S. et al. (2010). The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70–90 years. International Psychogeriatrics, 22, 12481264. doi: 10.1017/S1041610210001067.
Sachdev, P. S. et al. (2013). COSMIC (Cohort Studies of Memory in an International Consortium): an international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups. BMC Neurology, 13. doi: 10.1186/1471-2377-13-165.
Schmid, N. S., Taylor, K. I., Foldi, N. S., Berres, M. and Monsch, A. U. (2013). Neuropsychological signs of Alzheimer’s disease 8 years prior to diagnosis. Journal of Alzheimer’s Disease, 34, 537546. doi: 10.3233/JAD-121234.
Szamosi, A., Levy-Gigi, E., Kelemen, O. and Kéri, S. (2013). The hippocampus plays a role in the recognition of visual scenes presented at behaviorally relevant points in time: evidence from amnestic mild cognitive impairment (aMCI) and healthy controls. Cortex, 49, 18921900. doi: 10.1016/j.cortex.2012.11.001.
Vittinghoff, E., Glidden, D. V., Shiboski, S. C. and McCulloch, C. E. (2005). Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. Statistics for Biology and Health. New York: Springer.
Weintraub, S. et al. (2018). Version 3 of the Alzheimer Disease Centers’ neuropsychological test battery in the Uniform Data Set (UDS). Alzheimer Disease & Associated Disorders, 32, 1017. doi: 10.1097/WAD.0000000000000223.
Weissberger, G. H., Strong, J. V., Stefanidis, K. B., Summers, M. J., Bondi, M. W. and Stricker, N. H. (2017). Diagnostic accuracy of memory measures in Alzheimer’s dementia and mild cognitive impairment: a systematic review and meta-analysis. Neuropsychology Review, 27, 354388. doi: 10.1007/s11065-017-9360-6.
Winblad, B. et al. (2004). Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240246. doi: 10.1111/j.1365-2796.2004.01380.x.
Ye, B. S. et al. (2015). The heterogeneity and natural history of mild cognitive impairment of visual memory predominant type. Journal of Alzheimer’s Disease, 43, 143152. doi: 10.3233/JAD-140318.
Zammit, A. R., Ezzati, A., Zimmerman, M. E., Lipton, R. B., Lipton, M. L. and Katz, M. J. (2017a). Roles of hippocampal subfields in verbal and visual episodic memory. Behavioural Brain Research, 317, 157162. doi: 10.1016/j.bbr.2016.09.038.
Zammit, A. R. et al. (2017b). The association of visual memory with hippocampal volume. PLOS ONE, 12, e0187851. doi: 10.1371/journal.pone.0187851.
Zonderman, A. B., Giambra, L. M., Arenberg, D., Resnick, S. M., Costa, P. T. and Kawas, C. H. (1995). Changes in immediate visual memory predict cognitive impairment. Archives of Clinical Neuropsychology, 10, 111123. doi: 10.1093/arclin/10.2.111.


Type Description Title
Supplementary materials

Oltra-Cucarella et al. supplementary material
Table S1

 Word (15 KB)
15 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed